In the framework of an integral assessment (effectiveness and cost) of the use of neuroprotection in stroke, a cost-effectiveness study was conducted to compare the potential advantages of citicoline with conventional therapy (without neuroprotection or placebo) in patients with acute ischemic stroke. The literature was searched for systematic reviews and meta-analyses evaluating the effectiveness of citicoline versus placebo in the hospital setting and during 12 weeks after discharge from hospital. Data on the use of resources were obtained from a panel of experts of four acute-care teaching hospitals in Spain. The study was performed from the perspective of the Spanish National Health System. Two meta-analyses were included (Cochrane Stroke Review Group and a pooling analysis). Treatment with citicoline resulted in 99 or 50 more patients recovered per 1000 patients treated (depending on selection criteria of the Cochrane study and the pooled analysis), with average cost savings between euro101.2 and euro126.4 per patient treated of the type of those included in the Cochrane study. In patients with acute ischemic stroke, treatment with placebo was more expensive and less effective in the scenarios of inpatient care and inpatient plus outpatient care after discharge from the hospital.